Christopher Bunick, MD/PhD
Associate Professor of DermatologyCards
About
Research
Overview
Principal Investigator Background
Dr. Christopher Bunick, MD, PhD, is an Associate Professor of Dermatology performing dermatologic research studying the three-dimensional structures of skin-related proteins using primarily x-ray crystallography and cryo-electron microscopy. Dr. Bunick has over 25 years of experience in the field of structural biology. He leads a structural biology research program in the dermatology field, with a specific niche: “atomic resolution dermatology.” Dr. Bunick’s research focuses on determining the atomic resolution structures of proteins, protein complexes, and drug-ligand complexes that are essential to formation of a functional human skin barrier or the action of a precision medicine therapy. He uses x-ray crystallography and cryo-electron microscopy to: 1) determine the high resolution, three-dimensional structures of proteins important to both normal and diseased skin, and 2) determine the mechanism of action of how dermatology drugs bind their molecular target. Knowing the structure of various skin proteins and drugs enables a better understanding of how a protein or therapeutic functions in normal and diseased skin states. Ultimately, it may lead to the development of novel therapies or better patient care.
Areas of Active Basic Science Research
The Bunick lab applies biochemistry, structural biology (X-ray crystallography, Cryo-EM), and cell biology techniques to investigate biological processes of human skin. As a board-certified and practicing dermatologist, Dr. Bunick tackles scientific questions that can improve clinical care of patients. We have ongoing cutting edge translational research in the following areas:
1. Molecular mechanisms of intermediate filament (IF) assembly.
IFs, which include keratins, are fundamental filamentous assemblies that comprise the cellular cytoskeleton, regulate cellular signaling, and form an essential component of the human skin barrier. The Bunick lab discovered a novel assembly mechanism shared among IFs, and we continue to investigate the function of IFs.
2. Molecular mechanisms of human skin barrier integrity.
Keratin IFs regulate the human skin barrier through two key processes: i) filaggrin aggregation of keratins to form an impermeable proteinaceous barrier in the stratum corneum, and ii) keratins bind desmoplakin at desmosomes to enhance cell-cell adhesion in the epidermis. The Bunick lab has determined the only filaggrin structure and 75% of all keratin structures to date, and investigate the mechanisms of keratin assemblies in skin barrier function.
Two recent proteins studied are human profilaggrin and the keratin 1/10 complex because of their importance to skin barrier integrity and association with clinically relevant skin diseases. The NIH/NIAMS website estimates up to 90 million Americans suffer from some form of atopic dermatitis. Atopic dermatitis and other forms of severely dry skin, such as ichthyosis vulgaris, are associated with defects or mutations in profilaggrin and its processed fragment, filaggrin. Similarly, mutations mapped to keratins 1 or 10 are linked to several clinical disorders of keratinization (keratinopathies). Work on these proteins led to a 2.2 Å resolution crystal structure of the profilaggrin S100 calcium-binding domain and several 2.0 Å to 3.3 Å resolution crystal structures of complexes between the 1B and 2B helices of K1 and K10.
3. Acne vulgaris pathogenesis and mechanisms of drug therapy.
Building from our structure of the acne drug sarecycline bound to the 70S ribosome, we investigate how acne drugs function in their pathogenic target, Cutibacterium acnes, and how that impacts clinical efficacy and antibiotic resistance. We investigate how C. acnes regulates the microbiome niche of the pilosebaceous unit.
4. Molecular mechanisms of skin therapeutics in patient care.Dr. Bunick's lab works to understand the biochemical mechanisms of dermatologic drugs. Recent work on the structural mechanism of the acne vulgaris drug sarecycline was published in PNAS, and there are ongoing drug development projects in the lab in acne vulgaris, psoriasis, atopic dermatitis, cancer, and more.
Funding
Dr. Bunick currently is funded by the NIH/NIAMS (R01 Award) and a research grant from Almirall. His laboratory is open to medical students, graduate students, and post-docs motivated by and passionate for applying biochemistry and structural biology to skin disease.
Graduate & Medical Students, Post-docs, and Mentorship
Dr. Bunick's lab is committed to providing a highly intellectual and fun environment to develop the research skills necessary to succeed in life, whether in academia, industry, or elsewhere. We teach students the key processes used in our research, including protein production and purification, biochemical assays, structure determination techniques, and clinical/translational thinking. Dr. Bunick is faculty in the Yale Program in Translational Biomedicine, and participates in the BBS Track: Translational Molecular Medicine, Pharmacology, and Physiology (TMMPP).
Clinical Trials
Dr. Bunick works with the Yale Center for Clinical Investigation to lead clinical trial investigations on promising new dermatology therapeutics. Trials to date include:
Ongoing:
-VAPAUS: A Multicenter, Phase 3 Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of PTX-022 in the Treatment of Pachyonychia Congenita.
-TMB01-301: The ASCEND Study: A Phase III, Multicenter, Double Blinded Vehicle Controlled Study of TMB-001 - with a Parallel Optional Maximal Use Arm - in the Treatment of RXLI (X-linked) or ARCI Ichthyosis in Subjects Aged ≥ 6 Years.
Completed:
-A randomized, parallel, double-blind, vehicle-controlled study to evaluate the safety and efficacy of two different concentrations of topical TMB-001 for the treatment of congenital ichthyosis.
-A randomized, bilateral comparison, vehicle-controlled, safety and tolerability study of topical PAT-001 for the treatment of congenital ichthyosis.
Medical Subject Headings (MeSH)
Academic Achievements and Community Involvement
Clinical Care
Overview
Christopher Bunick, MD, PhD, is a dermatologist who enjoys seeing how happy his patients are when their skin conditions improve. “The confidence they gain to go out into the world and not be shy about the appearance of their skin makes me feel like I am making a difference in people's lives,” says Dr. Bunick, who sees patients in Dermatology’s Middlebury location.
Dr. Bunick treats patients of all ages for all conditions that affect the skin, hair and nails. These run the gamut from pinpointing the cause of a rash to treating eczema, psoriasis, skin lupus, pigment disorders and skin infections. He regularly performs dermatologic surgery for skin cancers and other benign lesions as well.
Having an open and truthful relationship with his patients is both important and deeply rewarding to Dr. Bunick. “First and foremost, I am always honest with my patients, whether the news I am giving them is positive or not. I always reassure them that I will work very hard to help them, even if it takes time to figure out the problem,” he says. “Patients are always welcome to call if they have any questions or concerns.”
When he’s not caring for his patients, Dr. Bunick, who is an associate professor of dermatology for Yale School of Medicine, conducts research on the three-dimensional protein structures that form the skin’s barrier. “My hope is to better understand the molecular mechanisms of the skin barrier, and translate that into better topical therapies for skin issues my patients face,” Dr. Bunick says.
Clinical Specialties
Fact Sheets
Acne (Acne Vulgaris)
Learn More on Yale MedicineViral Warts
Learn More on Yale MedicineSeborrheic Keratosis
Learn More on Yale MedicineRingworm (Tinea)
Learn More on Yale Medicine
Yale Medicine News
Links & Media
Media
- Acne vulgaris drug sarecycline binds to the 30S subunit of the bacterial ribosome (gray 16S-rRNA) as well as makes contact with mRNA through its unique C-7 moiety.
- The x-ray crystal structure of the complex between 2B helices of keratin 1 and keratin 10 is shown as a partial molecular surface (left) or partial ribbon diagram (right). The structure is suspended in front of an x-ray diffraction image (left) and a keratin crystal (right).
- The profilaggrin crystal structure suspended in front of four panels (upper left, immunofluorescence of profilaggrin localization; upper right, yeast-two-hybrid image for profilaggrin and annexin II interaction; lower left, crystals grown of profilaggrin; and lower right, an x-ray diffraction image collected on the profilaggrin crystals)
- Photo by Christopher Bunick
The structure of Cutibacterium acnes 70S ribosome with the antibiotic sarecycline bound, seen with Cryo-EM microscopy at atomic resolution.
News
- January 23, 2024
Dermatology Research Presented at Yale Life Sciences Pitchfest
- August 28, 2023Source: Practical Dermatology
Christopher G. Bunick, MD, PhD, Receives the American Acne and Rosacea Society's 2023 Research Scholar Award
- March 29, 2023Source: WTNH News 8
Health Headlines: Does the latest TikTok skin care trend really work?
- March 01, 2023
Antibiotics for Acne: Groundbreaking Study Shows Why One Works Best